D-Dimer as a Risk Factor for the Severity of COVID-19 Infection

Abstract

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a variable clinical course, and mortality risk factors are not well established. Methods: This retrospective study included adult inpatients (≥20 years old) with laboratory-confirmed COVID-19 from Al-Sadder Hospital and Alamal Hospital in Al-Najaf, Iraq. The patients either died or were discharged between December 1, 2021, and January 31, 2022. Data on demographics, clinical trials, treatments, and laboratory results were collected from the hospital database for both survivors and non-survivors. Statistical analyses were performed to identify the risk factors for in-hospital mortality. Results: A total of 100 patients were included in the study, of whom 67 were discharged and 33 died in the hospital. The age distribution showed that 45% of the patients were under 40 years of age, while 55% were over 40 years old. The cohort comprised 57% males (37 survivors vs. 20 non-survivors, p=0.024) and 43% females (30 survivors vs. 13 non-survivors, p=0.010). Comorbidities were present in 66% of the patients, with 55% of the survivors and 87% of the non-survivors having underlying conditions. Notably, diabetes mellitus was more prevalent in the non-survivors (85% vs. 18%), followed by asthma (58% vs. 10%), stroke (48% vs. 10%), renal failure (42% vs. 6%), heart attack (33% vs. 10%), and hypertension (18% vs. 15%). The findings revealed a median white blood cell (WBC) count of 8.7 mg/dl (IQR: 6.1–15.63 mg/dl), lymphocyte count of 57.6 (52.8–61.1), D-dimer levels of 2.35 μg/ml (IQR: 1.2–4.72 μg/ml), ferritin levels of 775 μg/ml (IQR: 720.3–866.4 μg/ml), C-reactive protein (CRP) levels of 4.55 mg/dl (IQR: 1.5–5.3 mg/dl), and lactate dehydrogenase (LDH) levels of 341.5 IU/L (IQR: 291.3–427 IU/L). These parameters were significantly higher in the non-survivors than in the survivors. A significant positive correlation was found between D-dimer and ferritin, CRP, and LDH as well as between WBC and lymphocyte counts and LDH. ROC analysis indicated that CRP had an area under the curve (AUC) of 0.802 (95% CI: 0.717-0.886) with a cutoff of 4.45 mg/dl, demonstrating 87.9% sensitivity and 37.3% specificity. D-dimer showed an AUC of 0.749 (95% CI: 0.652-0.846) with cutoff of 2.40 μg/ml, 81.8%, and 32.8%, respectively. LDH had an AUC of 0.70 (95% CI: 0.587-0.813) with a cutoff of 353.50 IU/L and 72.7% sensitivity and 37.3% specificity. Ferritin had the lowest AUC of 0.684 (95% CI: 0.555-0.813), with cutoff of 809.50 μg/ml, 69.7%, and 37.1%, respectively. Conclusion: This study found that older age correlates with elevated D-dimer, ferritin, CRP, and LDH levels. These parameters are associated with disease severity and mortality risk in adult COVID-19 patients. D-dimer and CRP levels have emerged as two of the most reliable predictors of disease progression. Understanding the interplay between these biomarkers and disease progression may lead to targeted therapeutic interventions and better resource allocation in healthcare settings.

Keywords: D-dimer, coronavirus disease, ferritin, receiver operating curve (ROC), area under the curve (AUC)